ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Parasite and Host
Enhancing the structural stability of P29-targeted monoclonal antibodies via β-hydroxybutyrylation modification improves their therapeutic performance in alveolar echinococcosis
Provisionally accepted
- 1Ningxia Medical University School of Basic Medicine, Yinchuan, China
- 2General Hospital of Ningxia Medical University, Yinchuan, China
- 3People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
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Abstract Alveolar echinococcosis (AE), a severe parasitic infection often likened to "parasitic cancer", still lacks effective treatments. Although our earlier work on the P29 monoclonal antibody (P29 mAb) against the parasite-derived P29 antigen showed potential, its efficacy remained limited, prompting the need for improved biologic agents. In this study, we applied β-hydroxybutyrylation (kbhb) modification to engineer an enhanced antibody, P29 mAbkbhb, and comprehensively evaluated its properties. Using surface plasmon resonance, protease resistance assays, pharmacokinetic studies in C57BL/6 mice, and histopathological analysis of alveolar hydatid cyst, we demonstrated that the modified antibody retains high antigen-binding affinity (KD = 343 pM) and exhibits markedly increased resistance to proteolytic degradation, with a 1.75-fold improvement in serum persistence after 5 weeks. Furthermore, in a murine model of AE, P29 mAbkbhb significantly inhibited protoscolex regeneration and induced apoptosis of cyst wall cells relative to the unmodified antibody. Our results establish a novel connection between protein engineering and antiparasitic therapy, illustrating that kbhb modification not only augments the efficacy of anti-AE antibodies but also offers a versatile strategy for enhancing antibody stability and half-life, thereby offering a potential strategy for developing new treatments against neglected zoonotic diseases via tailored post-translational modifications.
Keywords: Alveolar echinococcosis, antibody, Antiparasitic therapy, Protein Engineering, β-hydroxybutyrylation
Received: 30 Sep 2025; Accepted: 04 Dec 2025.
Copyright: © 2025 Yuan, Li, Niu, Zhu, Wu, Zhao, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wei Zhao
Ming Li
Zihua Li
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